Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia

Fernandez-Botran, Rafael; Uriarte, Silvia M.; Arnold, Forest W.; Rodriguez-Hernandez, Lisandra; Rane, Madhavi J.; Peyrani, Paula; Wiemken, Timothy; Kelley, Robert; Uppatla, Srinivas; Cavallazzi, Rodrigo; Blasi, Francesco; Morlacchi, Letizia; Aliberti, Stefano; Jonsson, Colleen; Ramirez, Julio A.; Bordon, Jose

The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10753-014-9840-2) contains supplementary material, which is available to authorized users.